The aim of this research is to study the effect of Annexin A2 SNP rs17845226 on vWF secretion by endothelial cells of controls carrying different Annexin A2 SNP rs17845226 genotypes (WT, homozygous, heterozygous). By testing several endothelial cell…
ID
Source
Brief title
Condition
- Coagulopathies and bleeding diatheses (excl thrombocytopenic)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
This study is a laboratory driven study. The main study endpoint is the
elucidation of the Annexin A2 dependent VWF secretion pathway.
Secondary outcome
N.A.
Background summary
Von Willebrand factor (vWF) is an adhesive protein essential for the arrest of
bleeding after vascular injury. vWF mediates the primary hemostatic response by
promoting platelet adhesion and platelet aggregation ultimately leading to the
formation of a primary hemostatic plug. Besides this, vWF also serves as a
carrier protein for the procoagulant clotting factor VIII and protects FVIII
from proteolysis. A deficiency of vWF results in the most common inherited
bleeding disorder named Von Willebrand disease (VWD).
Endothelial cells store vWF in Weibel Palade Bodies (WPB) and secrete vWF by
exocytosis of the WPB. The phospholipid binding protein Annexin A2 is involved
in the exocytosis of WPB in endothelial cells and thus the secretion of vWF.
Annexin A2 resides in a tight complex with the S1000A10 protein. Upon Ca²*
binding, WPB exocytosis in endothelial cells is stimulated. Recently the
Annexin A2 SNP rs17845226 (c.346G>T) is shown to be involved in lowering the
plasma vWF levels in controls. The effect of the Annexin A2 SNP rs17845226 on
vWF secretion by endothelial cells and the pathway involved is still unclear.
Study objective
The aim of this research is to study the effect of Annexin A2 SNP rs17845226 on
vWF secretion by endothelial cells of controls carrying different Annexin A2
SNP rs17845226 genotypes (WT, homozygous, heterozygous). By testing several
endothelial cell activation pathways the Annexin A2 dependent activation
pathway can be determined.
Study design
This design of our study is cross-sectional with a single collection of blood
samples and serves to find out whether the Annexin A2 SNP rs17845226 (c.346G>T)
has an influence on the vWF secretion by endothelial cells. We will obtain max.
36 ml of citrated blood from participants of a former Nijmegen Biomedical Study
(NBS), which are selected based on their Annexin A2 SNP rs17845226 (c.346G>T)
genotype (3 to 5 heterozygous participants, 3 to 5 homozygous participants, and
3-5 wild type (WT) participants.
Study burden and risks
The subjects will be asked to donate blood. A single blood collection of 36 ml
will be performed, for which the subjects will be specifically invited. The
patients will not be challenged by any other intervention. Therefore, we
anticipate that risks are negligible and the burden minimal in this study.
Geert Grooteplein Zuid 8
Nijmegen 6525 GA
NL
Geert Grooteplein Zuid 8
Nijmegen 6525 GA
NL
Listed location countries
Age
Inclusion criteria
- Participant of the Nijmegen Biomedical Study (NBS) with informed consent to be contacted for further research.
- Homozygous or heterozygous for the Annexin A2 SNP rs17845226 (c.346G>T), or WT.
Exclusion criteria
- No written informed consent for study participation obtained from the subject.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL57314.091.16 |